Aggrescan3D: Trp865 [mutate: TX865W]

Project name: Trp865 [mutate: TX865W]

Status: done

submitted: 2019-01-30 09:16:56, status changed: 2019-01-30 11:36:20

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Chain sequence(s)	X: EVTIKVNLIFADGKIQTAEFKGTFEEATAEAYRYADLLAKVNGEYTADLEDGGNHMNIKFA
Distance of aggregation	10 Å
Dynamic mode	Yes
Mutated residues	TX865W
Energy difference between WT (input) and mutated protein (by FoldX)	-0.151665 kcal/mol Changes in protein stability upon mutation are calculated using the FoldX forcefield. Computational prediction of protein stability is used with the intention of preventing the experimental characterization of proteins bearing mutations that significantly destabilize their structure. Mutations resulting in a predicted reduction in protein stability ≥ 1 kcal/mol are considered disruptive.

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Minimal score value: -2.7443
Maximal score value: 1.6623
Average score: -0.6632
Total score value: -39.7925

The table below lists A3D score for protein residues. Residues with A3D score > 0.0000 are marked by yellow rows.

residue index	residue name	chain	Aggrescan3D score	mutation
residue index	residue name	chain	Aggrescan3D score	mutation
820	E	X	-1.3571
821	V	X	-0.0355
822	T	X	-0.8663
823	I	X	0.0000
824	K	X	-2.1169
825	V	X	0.0000
826	N	X	-0.9060
827	L	X	0.0000
828	I	X	1.1105
829	F	X	0.7373
830	A	X	-0.2250
831	D	X	-1.8868
832	G	X	-1.1545
833	K	X	-1.2326
834	I	X	0.8207
835	Q	X	-0.0975
836	T	X	-0.5600
837	A	X	0.0000
838	E	X	-2.2335
839	F	X	-1.6206
840	K	X	-2.0434
841	G	X	-1.3037
842	T	X	-1.3202
843	F	X	-0.9467
844	E	X	-2.4201
845	E	X	-2.7443
846	A	X	0.0000
847	T	X	-1.3241
848	A	X	-1.3121
849	E	X	-1.7895
850	A	X	0.0000
851	Y	X	0.0198
852	R	X	-1.2972
853	Y	X	-0.3470
854	A	X	0.0566
855	D	X	-0.8948
856	L	X	-0.0090
857	L	X	0.0000
858	A	X	-0.8560
859	K	X	-1.1265
860	V	X	0.4928
861	N	X	-1.1134
862	G	X	-0.3688
863	E	X	-0.8955
864	Y	X	1.1229
865	W	X	1.4306	mutated: TX865W
866	A	X	0.7880
867	D	X	0.1126
868	L	X	0.1717
869	E	X	-2.1590
870	D	X	-2.7083
871	G	X	-1.9678
872	G	X	-1.4679
873	N	X	-1.5197
874	H	X	-1.6940
875	M	X	-0.5935
876	N	X	-0.3386
877	I	X	0.0000
878	K	X	0.5351
879	F	X	1.6623

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Above is the comparison between the input structure and the most aggregation prone model (predicted in the flexibility simulations, download both models in the PDB file format , download table with rmsd values ). The picture presents the most aggregation prone model (in blue) superimposed on the input structure (in red). The plot shows rmsd profile (distances between residues of the superimposed structures).

Dynamic mode uses CABS-flex simulations of protein structure fluctuations. The structure fluctuations may have impact on the size and extent of aggregation "hot-spots" on the protein surface. The dynamic mode uses the following pipeline: (1) based on the input structure, CABS-flex predicts a set of different models reflecting protein dynamics in solution; (2) for each of these models A3D score is calculated; (3) finally, the most aggregation prone model (the model with the highest A3D score, -0.6632 in this case) is selected and presented in A3D results.